The manganese(III) porphyrin MnTnHex-2-PyP5+ modulates intracellular ROS and breast cancer cell migration: Impact on doxorubicin-treated cells.

dc.contributor.author

Flórido, Ana

dc.contributor.author

Saraiva, Nuno

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Cerqueira, Sara

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Almeida, Nuno

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Parsons, Maddy

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Batinic-Haberle, Ines

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Miranda, Joana P

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Costa, João G

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Carrara, Guia

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Castro, Matilde

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Oliveira, Nuno G

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Fernandes, Ana S

dc.date.accessioned

2020-07-15T22:16:45Z

dc.date.available

2020-07-15T22:16:45Z

dc.date.issued

2019-01

dc.date.updated

2020-07-15T22:16:42Z

dc.description.abstract

Manganese(III) porphyrins (MnPs) are superoxide dismutase (SOD) mimics with demonstrated beneficial effects in cancer treatment in combination with chemo- and radiotherapy regimens. Despite the ongoing clinical trials, little is known about the effect of MnPs on metastasis, being therefore essential to understand how MnPs affect this process. In the present work, the impact of the MnP MnTnHex-2-PyP5+ in metastasis-related processes was assessed in breast cancer cells (MCF-7 and MDA-MB-231), alone or in combination with doxorubicin (dox). The co-treatment of cells with non-cytotoxic concentrations of MnP and dox altered intracellular ROS, increasing H2O2. While MnP alone did not modify cell migration, the co-exposure led to a reduction in collective cell migration and chemotaxis. In addition, the MnP reduced the dox-induced increase in random migration of MDA-MB-231 cells. Treatment with either MnP or dox decreased the proteolytic invasion of MDA-MB-231 cells, although the effect was more pronounced upon co-exposure with both compounds. Moreover, to explore the cellular mechanisms underlying the observed effects, cell adhesion, spreading, focal adhesions, and NF-κB activation were also studied. Although differential effects were observed according to the endpoints analysed, overall, the alterations induced by MnP in dox-treated cells were consistent with a therapeutically favorable outcome.

dc.identifier

S2213-2317(18)30848-6

dc.identifier.issn

2213-2317

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2213-2317

dc.identifier.uri

https://hdl.handle.net/10161/21188

dc.language

eng

dc.publisher

Elsevier BV

dc.relation.ispartof

Redox biology

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10.1016/j.redox.2018.10.016

dc.subject

Cell Line, Tumor

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Intracellular Space

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Humans

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Breast Neoplasms

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Reactive Oxygen Species

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Metalloporphyrins

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Doxorubicin

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NF-kappa B

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Cell Adhesion Molecules

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Cell Adhesion

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Cell Movement

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Cell Survival

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Gene Expression Regulation

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Molecular Structure

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Female

dc.title

The manganese(III) porphyrin MnTnHex-2-PyP5+ modulates intracellular ROS and breast cancer cell migration: Impact on doxorubicin-treated cells.

dc.type

Journal article

pubs.begin-page

367

pubs.end-page

378

pubs.organisational-group

School of Medicine

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Radiation Oncology

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Duke

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Clinical Science Departments

pubs.publication-status

Published

pubs.volume

20

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